Anemia is highly prevalent in late stages of Chronic Kidney Disease (CKD). Twenty million American adults have CKD and millions of others are at increased risk, a scenario that is increasingly viewed as a 'silent' epidemic worldwide. The administration of Erythropoiesis Stimulating Agents (ESAs) has significantly decreased the transfusion related complications and improved patient quality of life. Increased use of ESA's has also led to recognition of their limitations by virtue of observed adverse events. Recently, the FDA issued a modified recommendation for dosing of ESA's in CKD, and ruled that anemia management in CKD should be individualized to minimize the patient ESA exposure and at the same time prevent transfusions. It is generally understood that anemia management protocols (AMPs) which guide ESA dosing, and until now have been designed using standardized 'one-size-fits-all' approach, will have a crucial role in achieving this goal. The applicant is seekinga K25 Mentored Quantitative Research Career Development award for the purpose of establishing an independent research career at the interface of engineering and medicine. The applicant's academic training is in Mechanical Engineering with specific emphasis in system dynamics and feedback control. He has established a track record of high quality publications, mentoring students, and winning multiple research funding awards. His research focus has shifted in recent years to collaborations with physicians. Under the co-mentorship of Drs. Germain (Baystate Health) and Thadhani (Massachusetts General Hospital), the applicant will engage in a rigorous academic training in relevant topics from physiology through biostatistics and epidemiology, and the responsible conduct of research. The goals of the proposed research are: (1) improvement and validation of an erythropoiesis model that the applicant has created, and, building upon this model, (2) development of a design framework for individualized Anemia Management Protocols that address the new FDA recommendation. By integrating proven engineering methodologies and current knowledge about ESA's role in treatment of anemia of End Stage Renal Disease (ESRD), the applicant proposes to create a new paradigm for designing individualized AMP's. Such AMPs will serve as decision support tools to the physician and will be applicable not only to currently available ESA's but also to other chronically administered drugs. Anemia is highly prevalent in Chronic Kidney Disease (CKD). Twenty million American adults have CKD and millions of others are at increased risk, a scenario that is increasing viewed as a 'silent' epidemic worldwide. This project will result in a new framework for designing individualized anemia management protocols which will provide physicians with decision support to improve treatment outcomes.